Evaluating the treatment efficacy of novel Leads against drug resistant and high threat bacterial agents in animal models is crucial for advancing compounds to the preclinical stage of development. Currently, there is a paucity of reproducible disease models with reliable metrics to assess lead compounds and even less facilities and personnel to perform such important studies. To meet this important challenge, the Animal core for this proposed CETR has developed reproducible wound, systemic and pulmonary infection models in rodents for multidrug resistant bacteria of clinical significance and high threat select agents. The Aims ofthe core are to: 1 provide small animal infection models for ESKAPE, TB and select agent bacterial pathogens to evaluate lead compounds, and 2) provide state ofthe art analytical services on host response and bacterial bio-burden distribution to assess and quantify lead compound treatment efficacy. The Animal core under the direction of Dr. Perlin has served as a multi-institutional regional animal core for the Region II RCE (Northeast Biodefense Center) for the past 9 years, and routinely works with numerous investigators for evaluation of therapeutic countermeasures. It is a highly active core having logged more than 1.2 million animal days of BSL3 agents. A highly experienced and dedicated animal model team performs a wide range of infection models with multiple routes of infections (iv, oral, aerosol, subcutaneous, mucosal) and markers for disease (morbidity/mortality, microbial burden, histopathology, etc.) Furthermore, the Animal core possesses cutting edge instrumentation for analysis of infections and therapeutic responses. The incorporation of reproducible animal models operated by highly experienced staff and utilizing novel technologies will advance and accelerate the development of promising Lead compounds against multidrug resistant and high threat bacterial agents. All services can be performed under high-level biocontainment with regulatory approval.